Transcription:
All About GBS Infection

Dr. Joti Sharma: Hello, everyone. And welcome back to another edition of Neonatology Review: Isolette to Crib I'm Dr. Joti Sharma, and I will be your host for this episode. The purpose of this podcast is to review high-yield common topics in neonatology. While our focus is geared towards the perinatal and neonatal boards, anyone learning or studying neonatology will find this podcast useful.

For this episode, our guest is Dr. Sanjay Akangire, who is a neonatologist with us here at Children's Mercy Hospital in Kansas City. Tell hi to everyone, Dr. Akangire.

Dr. Sanjay Akangire: Hi, everyone. This is Dr. Akangire. And thank you, Dr. Sharma, for inviting. And it's a pleasure to be here.

Dr. Joti Sharma: And he is joining us today to talk about all you need to know about group B streptococcus infection or GBS. In this episode, we will cover the epidemiology, pathogenesis and management of GBS infection. So Dr. Akangire, to start off, let's talk about the incidence and epidemiology of group B strep.

Dr. Sanjay Akangire: Sure, Dr. Sharma. So in the US, incidence of GBS disease was approximately two cases per 1000 live births in 1990s and early two thousands. This has decreased to approximately 0.5 cases per 1000 live births by 2016. And this decline is mostly for early-onset GBS disease. And Dr. Sharma, important point to remember that this overall decline is on early-onset GBS disease and has been due to universal screening of pregnant women for GBS colonization and widespread use of intrapartum antibiotic prophylaxis or IAP.

Dr. Joti Sharma: Dr. Akangire, thanks for that review. And as you mentioned, there has been a dramatic decrease in early-onset GBS disease just with the universal intrapartum antibiotic prophylaxis. And that has been remarkable. So how about late-onset GBS infection? What is the incidence and epidemiology of that?

Dr. Sanjay Akangire: Yes. So the incidence of lateonset GBS disease in the United States has remained unchanged since 1990s. And it's approximately 0.3 to 0.4 cases per 1000 live births. This may be an important point to know for neonatal boards and in clinical practice as well that African-American infants are at higher risk of infection than white infants. And the rate is about 0.6 versus 0.2 cases per 1000 live births.

Dr. Joti Sharma: That is a good summary of the incidence of GBS infection. Can you talk about the risk factors for GBS infection?

Dr. Sanjay Akangire: Sure. So the primary risk factor for early onset GBS infection is maternal colonization of GBS in genitourinary or gastrointestinal system. And the rate of transmission from colonized mother to infants without intrapartum antibiotic prophylaxis is about 50%, but only 1% to 2% of all infants born to colonized pregnant women end up having early-onset GBS disease.

And Dr. Sharma, some of the other risk factors for GBS early-onset sepsis are delivery at less than 37 weeks' gestation, if the rupture of membranes is prolonged or more than 18 hours prior to delivery, intraamniotic infection as we talked in our previous podcast, GBS bacteriuria during current pregnancy, prior history with GBS disease or prior infant with GBS disease, temperature of 38.4 or greater during labor and premature rupture of membranes.

There are 10 GBS serotypes and knowing some of these may be be important for neonatology boards. Serotypes 1a, 1b, 2, 3 and 5 are responsible for majority of both early and late-onset GBS infections. And serotype 3 tends to cause meningitis.

Dr. Joti Sharma: Oh, yes. Thanks for covering the risk factors for GBS early-onset sepsis, and that can also appear on the neonatal board. So that's a great summary you just did. So, as you mentioned earlier, about intrapartum antibiotic prophylaxis playing a big role in the reduction of early-onset GBS infection, would you mind talking more about the intrapartum antibiotic prophylaxis?

Dr. Sanjay Akangire: Sure. Dr. Sharma, very important topic. ACOG recommends targeted IV intrapartum antibiotic prophylaxis in prevention of GBS early-onset disease. All pregnant women should get antepartum GBS screening between 36 to 37 weeks and six days of gestation. If positive, should get intrapartum prophylaxis unless there is C-section performed without labor in the setting of intact membranes.

Women with positive GBS culture undergoing C-section prior to onset of labor with intact membranes does not require GBS prophylaxis. If GBS is unknown when labor starts and intrapartum prophylaxis is indicated for women with risk factors like PPROM or rupture of membranes for greater than 18 hours or intrapartum fever of greater than a 100.4 for GBS early-onset disease.

If GBS is unknown when labor starts and no risk factors are present, but has history of GBS colonization in previous pregnancy, that mother may need intrapartum prophylaxis.

Dr. Joti Sharma: So aren't there two other indications for intrapartum antibiotic GBS prophylaxis? Do you mind going over those two? Because they also can appear on neonatology boards.

Dr. Sanjay Akangire: Absolutely. You are correct, Dr. Sharma. Apart from these recommendations for prophylaxis, two other situations intrapartum GBS prophylaxis is indicated, previous history of invasive GBS infection in sibling and GBS bacteriuria in this pregnancy.

Dr. Joti Sharma: So moving on, what is the antibiotic of choice for intrapartum antibiotic prophylaxis if the mom is GBS positive and needs prophylaxis?

Dr. Sanjay Akangire: IV penicillin or IV ampicillin remains the choice of antibiotics. In practice, most of the mothers end up getting IV ampicillin. In situations with concerns for anaphylaxis, first-generation cephalosporins are used with low risk of anaphylaxis. Clindamycin is used for high risk of anaphylaxis, and that is only if GBS is known to be susceptible to clindamycin. In the situation of high risk of penicillin allergy and if the GBS isolate is not susceptible to clindamycin, high dose IV vancomycin is recommended.

Dr. Joti Sharma: Thanks for that information, Dr. Akangire. Can we now move on to the pathogenesis of early-onset GBS sepsis, if you mind talking about that?

Dr. Sanjay Akangire: Sure, Dr. Sharma. Very important for neonatal boards again. So neonatal GBS infection is acquired while fetus is intrauterine through intraamniotic infection, rupture of membranes or ascending through the vaginal canal. GBS also appears to be capable of traversing through the intact membranes. Once GBS enters in amniotic fluid, it replicates and fetus can aspirate into lungs causing invasive disease in utero.

Exposure to GBS may occur during birth process while direct contact between the infant and the vaginal mucosal surface. After discharged from the hospitals, infants also can acquire GBS from colonized contacts and can manifest as late-onset bacteremia, meningitis, or other localized infections.

Dr. Joti Sharma: That's such a good summary. Now, let's move to the clinical manifestations of GBS disease. How about divided into the early and late-onset disease?

Dr. Sanjay Akangire: Sure. I'll start with early-onset disease. So most early-onset GBS disease occurs within the first 24 hours of birth. Early-onset GBS disease is considered when onset is within the first week of life. And in most cases, early-onset GBS manifests as sepsis without a focus in approximately 80%. And less common presentations are pneumonia, which is approximately 10% and meningitis is again approximately 10%.

Dr. Joti Sharma: Yes. And that is such an important point because early-onset GBS infection is infection usually without a focus. So how about late-onset GBS disease? What's different?

Dr. Sanjay Akangire: So late-onset GBS occurs after the first postnatal week. And routes of transmission in late-onset GBS infection are not very well understood. Late-onset GBS disease typically manifests as bacteremia without focal infection in approximately 60% to 65%. Less common presentations are bone or soft tissue infections and that includes osteomyelitis and septic arthritis or menigitis. Late-onset GBS meningitis may lead to vascular complications like arterial ischemic stroke and venous thrombosis, and also that contributes to poor neurologic outcomeS.

Dr. Joti Sharma: Now that we've talked about the pathogenesis, let's move to evaluation. So can we talk about the important aspects of evaluation of a newborn with suspected GBS disease?

Dr. Sanjay Akangire: Yes. So with any newborn, there should be a low threshold for evaluation and empiric treatment of possible early-onset GBS disease. This is due to possible morbidity including death. It's important to go over the risk factors for GBS disease, and that includes time of rupture of membranes, GBS status on mother, GBS prophylaxis if mother received that, gestational age, maternal intraamniotic infection and infant's clinical condition.

And Dr. Sharma, important thing to remember during evaluation is that the GBS testing time in mother is approximately at 36 weeks' of gestation to catch most women for GBS colonization. But there's still a chance of maternal GBS colonization between that testing time and the time of delivery. So that should be kept in mind during the evaluation.

Using neonatal sepsis calculator should be highly considered, and many institutions are using that in current era. In infants with ill-appearing exam, bacterial sepsis should be strongly suspected and infant should undergo a full diagnostic evaluation and antibiotics should be started empirically and continued for at least 48 hours if the blood culture is negative. For further details, please refer to our previous podcast on early-onset sepsis.

Dr. Joti Sharma: Dr. Akangire, I want to thank you for bringing up a very important point that even if maternal testing at 36 weeks is negative for GBS, it doesn't mean that at 40 weeks, the infant is not at risk of GBS infection. So if a baby is clinically symptomatic, we should always consider GBS as a differential. That was a good summary on the evaluation of an infant with suspected GBS. How about the management of infants with GBS infection?

Dr. Sanjay Akangire: So anti-microbial therapy and stabilizing the infant is a key in management of these infants. Supportive care includes ventilator support, fluid and electrolyte management, hemodynamic stabilization for septic shock and anemia and seizure control if infant has seizures. Empiric anti-microbial therapy should be broader to cover GBS, other streptococci, Gram-negative organisms and Listeria monocytogenes. Ampicillin and gentamicin should cover all of these organisms above and our preferred antibiotic choices.

Once GBS is identified, anti-microbial therapy should be changed to penicillin G or ampicillin, which is acceptable and equally effective. Lumbar punctures should be performed for CSF evaluation to rule out neonatal GBS meningitis. And brain MRI is warranted for infants with GBS meningitis to rule out brain abscess formation during the antibiotic use. And if infant had complicated GBS meningitis, MRI brain is needed again after the antibiotic therapy is done.

And IV antibiotics are administered for 10 days for bacteremia without a focus, 14 to 21 days for meningitis, 21 to 28 days for osteomyelitis and 14 to 21 days for septic arthritis. And in some situations, surgical drainage is needed for infants with septic arthritis in addition to antibiotics. And recurrent GBS infections are uncommon, but cases related to infected breastmilk have been reported.

Dr. Joti Sharma: Dr. Akangire, you have discussed some very important aspects of GBS infection. Can you please summarize the final key points for GBS?

Dr. Sanjay Akangire: Sure, Dr. Sharma. Universal screening and intrapartum antibiotic prophylaxis has substantially reduced early-onset GBS disease. GBS remains a major cause of both early-onset and late-onset neonatal sepsis. Early-onset GBS and late-onset GBS has distinct clinical presentations and sometimes diagnosis may be challenging. GBS infections, particularly meningitis, may have high mortality rate and may cause substantial morbidity in survivors.

Dr. Joti Sharma: So to end this episode, I wonder if you have come with some questions?

Dr. Sanjay Akangire: Yes. I have a couple of questions, very nice questions. So let's go with the first question. And the question is: You are discussing early onset group B strep infection and the clinical manifestations of the disease with some residents and fellows, which of the following is the most common manifestation of early-onset GBS disease in newborns? And the choices are: A, osteomyelitis and septic arthritis; B, meningitis; C, pneumonia; D, sepsis without a focus; E, urinary tract infection; and F, omphalitis. What do you think, Dr. Sharma?

Dr. Joti Sharma: Okay. I think you just mentioned that 80% of early-onset GBS disease is sepsis without a focus. Therefore, the answer I think is D. Am I correct?

Dr. Sanjay Akangire: Absolutely correct, Dr. Sharma. So sepsis without a focus is the answer. And as you said, in vast majority of cases, early-onset GBS manifests as a sepsis without a focus and pneumonia is about 10% and meningitis is about 10% in the presentation.

Dr. Joti Sharma: Yeah. And this is again a very important question that can appear on the neonatal boards. Do you have another question?

Dr. Sanjay Akangire: Yeah, I have one more question, which is relatively short compared to the previous one. So everything is related to GBS except-- you have to rule out-- so A is vaginal colonizations increases with age; B, greater risk of infection with prolonged rupture of membranes and prematurity; C, acquired by transplacental route; and D, penicillin is the ideal treatment in infants with GBS infection. What do you think, Dr. Sharma?

Dr. Joti Sharma: So this is all of these are true for GBS, except. You know, I think the answer here is C, it's not acquired by transplacental route. It is an ascending infection. Am I correct?

Dr. Sanjay Akangire: Absolutely correct, Dr. Sharma. So GBS is acquired through colonization during passage through vaginal canal or by ascending after rupture of membranes. And it's never acquired by transplacental route. But Dr. Sharma, I have a question for you. Do you know which organism is acquired through transplacental route in early-onset sepsis? Because there's a list of organisms which can cause early onset sepsis. So there's one important organism, which is known for causing the infection by transplacental route.

Dr. Joti Sharma: Yes, I think I know that, Dr. Akangire, and it is Listeria monocytogenes. Am I correct?

Dr. Sanjay Akangire: Absolutely correct. And I'm sure there's more details to share about Listeria, but you're absolutely correct. It's Listeria monocytogenes, which is acquired by transplacental route.

Dr. Joti Sharma: Well, thanks for bringing up Listeria, because in one of our future podcasts, we will actually discuss Listeria in detail. So thanks for that. Hopefully, this information will give you a better understanding of GBS infection in newborns. Until next time, this is Neonatology Review: Isolate to Crib. I'm Dr. Jyoti Sharma. Thanks for listening.